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Biodegradable Manganese-Doped Calcium Phosphate Nanotheranostics for Traceable Cascade Reaction-Enhanced Anti-Tumor Therapy
journal contribution
posted on 2019-12-13, 01:29 authored by Lian-Hua Fu, Yan-Ru Hu, Chao Qi, Ting He, Shanshan Jiang, Chao Jiang, Jin He, Junle Qu, Jing Lin, Peng HuangGlucose oxidase (GOx) has been recognized as a “star”
enzyme catalyst involved in cancer treatment in the past few years.
Herein, GOx is mineralized with manganese-doped calcium phosphate
(MnCaP) to form spherical nanoparticles (GOx-MnCaP NPs) by an in situ biomimetic mineralization method, followed by the
loading of doxorubicin (DOX) to construct a biodegradable, biocompatible,
and tumor acidity-responsive nanotheranostics for magnetic resonance
imaging (MRI) and cascade reaction-enhanced cooperative cancer treatment.
The GOx-driven oxidation reaction can effectively eliminate intratumoral
glucose for starvation therapy, and the elevated H2O2 is then converted into highly toxic hydroxyl radicals via a Mn2+-mediated Fenton-like reaction for
chemodynamic therapy (CDT). Moreover, the acidity amplification due
to the gluconic acid generation will in turn accelerate the degradation
of the nanoplatform and promote the Mn2+–H2O2 reaction for enhanced CDT. Meanwhile, the released
Mn2+ ions can be used for MRI to monitor the treatment
process. After carrying the anticancer drug, the DOX-loaded GOx-MnCaP
can integrate starvation therapy, Mn2+-mediated CDT, and
DOX-induced chemotherapy together, which showed greatly improved therapeutic
efficacy than each monotherapy. Such an orchestrated cooperative cancer
therapy demonstrated high-efficiency tumor suppression on 4T1 tumor-bearing
mice with minimal side effects. Our findings suggested that the DOX-loaded
GOx-MnCaP nanotheranostics with excellent biodegradability and biocompatibility
hold clinical translation potential for cancer management.
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4 T 1 tumor-bearing micetumor acidity-responsive nanotheranosticsTraceable Cascade Reaction-Enhanced Anti-Tumor Therapy Glucose oxidaseMRIcancer treatmentGOx-driven oxidation reactionmanganese-doped calcium phosphateBiodegradable Manganese-Doped Calcium Phosphate NanotheranosticsNPCDTH 2 O 2biomimetic mineralization methodhigh-efficiency tumor suppressionstarvation therapygluconic acid generationDOX-loaded GOx-MnCaP nanotheranostics
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